Dose-Dependent Effects of Interleukin-1Alpha on Functional Degradation of Lateral and Medial Menisci

2010 ◽  
Author(s):  
Carrie H. Ling ◽  
Janice H. Lai ◽  
James F. Nishimuta ◽  
Marc E. Levenston
Keyword(s):  
Interleukin 1 ◽  
Cartilage Degeneration ◽  
Meniscal Extrusion ◽  
Knee Oa ◽  
Degenerative Lesion ◽  
Disease Modifying Treatment ◽  
Dose Dependent ◽  
Meniscal Degeneration ◽  
Pro Inflammatory Cytokines

Despite a growing recognition that meniscal degeneration often precedes cartilage degeneration in the development of knee osteoarthritis (OA), little is known about the role of meniscal degeneration in the onset and progression of knee OA. Even a mild degenerative lesion increases meniscal extrusion, implying changes in biomechanical function. Understanding the mechanisms of meniscal degeneration may enable the diagnosis and disease-modifying treatment of early knee OA, potentially preventing or slowing the progression of the disease. The roles of pro-inflammatory cytokines such as interleukin-1 (IL-1) in promoting cartilage matrix degradation and mediating inflammation in the progression of OA have been widely demonstrated [1,2]. Recent results from our group indicated that 20ng/ml hrIL-1α produced similar cell-mediated degradation and loss of mechanical properties in immature cartilage and meniscus, but progresses more rapidly in meniscus explants [3]. This study further explored the effects of IL-1α dosage and medial-lateral differences on the functional degradation of meniscal explants.

The Updated Role of Ultrasound in the Assessment of Knee Osteoarthritis

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Khalid Esmat Alaam ◽  
Hazem Ibrahim Abd El Rahman ◽  
Nouran Saieed Ahmed
Keyword(s):  
Knee Osteoarthritis ◽  
Clinical Examination ◽  
Structural Damage ◽  
Cartilage Degeneration ◽  
University Hospitals ◽  
Meniscal Extrusion ◽  
Clinical Criteria ◽  
Knee Effusion ◽  
Monitoring Therapy ◽  
Meniscal Degeneration

Abstract Background Osteoarthritis (OA) of the knee is the most common form of knee arthritis and a leading cause of chronic disability. Objective The aim of the current study is to reassess the utility of the updated ultrasound in the patients with knee osteoarthritis and outline its clinical application. Patients and Methods The studied group included 36 patient 23females and 13 males with their ages ranged between 39 and 58 years (average age 44 years). The patients were referred to US examination fulfilling the ACR clinical criteria for knee OA after orthopedic and /or rheumatologist consultation. The study was performed in Radiodiagnosis department Ain Shams University Hospitals (20 patients ) and at one private center (16 patients). Results There was a discrepancy between the results obtained by clinical examination and those demonstrated by ultrasonography. Clinical examination detected 22 (61.1%) of our cases. Prevalence of US findings in our cases were femoral articular degeneration in 28 (77.7%) patients, Tibiofemoral osteophytes were seen in 26 patients (72.2%), knee effusion in 22 patients (61.1%),meniscal extrusion in 22 patients (61.1%) meniscal degeneration in 17 patients (47.2%) and synovial hypertrophy in 15patients (41.6%). Baker’s cysts were demonstrated in 14patients (38.8%) while pes anserine syndrome was demonstrated in 4 cases. Meniscal degeneration and meniscal extrusion were correlated significantly with femoral cartilage degeneration (P<.001). Although knee effusion did not correlate with advanced knee effusion did significantly (P > 0.05). Baker's cysts is statistically related to the presence and severity of mensical changes and also related to the degree of femoral articular cartilage degeneration. Conclusion US is a valuable technique that can assess soft tissue structures within the knee and their involvement in the osteoarthritic process .US enables in guiding and monitoring therapy through detection of knee structural damage.

scholarly journals Oral administration of EP4-selective agonist KAG-308 suppresses mouse knee osteoarthritis development through reduction of chondrocyte hypertrophy and TNF secretion

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yasutaka Murahashi ◽  
Fumiko Yano ◽  
Ryota Chijimatsu ◽  
Hideki Nakamoto ◽  
Yuji Maenohara ◽  
...  
Keyword(s):  
Oral Administration ◽  
Cartilage Degeneration ◽  
Necrosis Factor Alpha ◽  
Chondrocyte Hypertrophy ◽  
Knee Oa ◽  
Selective Agonist ◽  
Histone Deacetylase 4 ◽  
Factor Alpha ◽  
Disease Modifying Treatment ◽  
Tnf Secretion

AbstractOsteoarthritis (OA) is one of the world’s most common degenerative diseases, but there is no disease-modifying treatment available. Previous studies have shown that prostaglandin E2 (PGE2) and PGE2 receptor 4 (EP4) are involved in OA pathogenesis; however, their roles are not fully understood. Here, we examined the efficacy of oral administration of KAG-308, an EP4-selective agonist, in surgically induced mouse knee OA. Cartilage degeneration and synovitis were significantly inhibited by the KAG-308 treatment. Chondrocyte hypertrophy and expression of tumor necrosis factor alpha (TNF) and matrix metalloproteinase 13 (Mmp13) in the synovium were suppressed in the KAG-308-treated mice. In cultured chondrocytes, hypertrophic differentiation was inhibited by KAG-308 and intranuclear translocation of histone deacetylase 4 (Hdac4) was enhanced. In cultured synoviocytes, lipopolysaccharide (LPS)-induced expression of TNF and Mmp13 was also suppressed by KAG-308. KAG-308 was detected in the synovium and cartilage of orally treated mice. TNF secretion from the synovia of KAG-308-treated mice was significantly lower than control mice. Thus, we conclude that oral administration of KAG-308 suppresses OA development through suppression of chondrocyte hypertrophy and synovitis. KAG-308 may be a potent candidate for OA drug development.

The role of cytokines in the lipopolysaccharide-induced sick euthyroid syndrome in mice

1995 ◽  
Vol 146 (3) ◽  
pp. 475-483 ◽  
Author(s):  
A Boelen ◽  
M C Platvoet-ter Schiphorst ◽  
O Bakker ◽  
W M Wiersinga
Keyword(s):  
Single Dose ◽  
Synergistic Effects ◽  
Interleukin 1 ◽  
Lethal Dose ◽  
Acute Administration ◽  
Dependent Manner ◽  
Dose Dependent ◽  
Serum Tsh ◽  
Sick Euthyroid

Abstract To evaluate the role of cytokines in the sick euthyroid syndrome, we tried to establish an animal model of non-thyroidal illness in mice by the administration of a sub-lethal dose of bacterial endotoxin (lipopolysaccharide; LPS) which induces a variety of cytokines, including tumour necrosis factor (TNFα), interleukin-1 (IL-1α), interleukin-6 (IL-6) and interferon-γ (IFNγ). When compared with pair-fed controls, a single dose of LPS resulted in (a) systemic illness, (b) induction of TNFα and IL-6 and (c) a decrease of liver 5′-deiodinase mRNA from 4 h onwards followed by a decrease of serum tri-iodothyronine (T3) and thyroxine (T4) at 8 h and of serum free T3 (fT3) and free T4 (fT4) at 24 h; serum TSH remained unchanged. We then studied whether a single dose or a combination of IL-1α, TNFα, IL-6 or IFNγ could induce the sick euthyroid syndrome in mice, again using pair-fed controls. None of the cytokines except IL-1α caused systemic illness, and IL-1α was the only cytokine that decreased liver 5′-deiodinase mRNA transiently. IL-1α, TNFα or IL-6 did not decrease serum T3, T4 and TSH, but administration of IFNγ decreased serum T4, T3 and fT3 in a dose-dependent manner without changes in serum TSH. Administration of all four cytokines together had no synergistic effects; observed changes were of a smaller magnitude than after LPS. The following conclusions were reached. (1) Administration of LPS in mice is a suitable experimental model for the acute induction of the sick euthyroid syndrome. (2) Acute administration of IL-1α, TNFα or IL-6 in mice does not induce changes in thyroid hormones but IFNγ results in a dose-dependent decrease of serum T4, T3 and fT3 and IL-1α decreases liver 5′-deiodinase mRNA transiently. (3) Combined administration of IL-1α, TNFα, IL-6 and IFNγ had no synergistic effects; observed changes were of a smaller magnitude than after LPS. (4) The LPS-induced sick euthyroid syndrome is currently best explained by a direct thyroidal inhibition due to IFNγ and an extrathyroidal inhibition of liver 5′-deiodinase due to IL-1α, but other still unidentified factors seem to be involved as well. Journal of Endocrinology (1995) 146, 475–483

scholarly journals The Role of Interleukin in Ectopic Pregnancy: A Systematic Review

2021 ◽  
Vol 9 (F) ◽  
pp. 238-245
Author(s):  
Cahyono Hadi ◽  
Jethro Budiman ◽  
Awal Prasetyo ◽  
Cipta Pramana
Keyword(s):  
Ectopic Pregnancy ◽  
Interleukin 1 ◽  
Risk Of Bias ◽  
Lead Author ◽  
Database Searching ◽  
Exclusion Criteria ◽  
Diagnostic Significance ◽  
Cutoff Levels ◽  
Pro Inflammatory Cytokines

BACKGROUND: Ectopic pregnancy (EP) is the implantation of an embryo outside the eutopic cavity with the most location of EP is in the fallopian tube (FT), known as tubal EP (TEP). The FT of TEP expresses higher levels of pro-inflammatory cytokines such as interleukin-1 (IL-1), IL-6, and IL-8. AIM: The study aimed to look systematically into the current literature and carefully analyze the results to explore the role of IL in EP. METHODS: Three independent reviewers conducted the literature search through some electronic databases searching for articles fulfilling inclusion and exclusion criteria. The lead author independently assessed the risk of bias of each of the 313 articles identified in database searching, 12 articles met the criteria for this review. CONCLUSION: IL-6 and IL-8 have diagnostic significance in predicting EP with the cutoff levels of IL-6 and IL-8 which were 26.48 and 40 pg/mL. Further, research is needed for the role of other interleukins in EP.

IL-1β and IL-1ra are key regulators of the inflammatory response to RNA vaccines

2021 ◽  
Author(s):  
Ira Mellman ◽  
Siri Tahtinen ◽  
Ann-Jay Tong ◽  
Patricia Himmels ◽  
Jaehak Oh ◽  
...  
Keyword(s):  
Adverse Events ◽  
Systemic Inflammation ◽  
Viral Infections ◽  
Inflammatory Responses ◽  
Interleukin 1 ◽  
Inflammatory Stimuli ◽  
Dose Dependent ◽  
Systemic Responses ◽  
Pro Inflammatory Cytokines

Abstract Excessive systemic inflammation is characteristic to various acute conditions including sepsis, viral infections and immunotherapy-induced adverse events such as cytokine release syndrome (CRS). Recently, several clinical trials evaluating variants of lipid-formulated RNA vaccines for either cancer or COVID-19 have reported systemic inflammatory responses that limit vaccine dosing in humans. Preclinical studies in inbred laboratory mice failed to predict these adverse events, suggesting the existence of underlying differences in sensitivity to Toll-like receptor (TLR) or other innate agonists between humans and mice. Here, we identify interleukin 1 receptor antagonist (IL-1ra) as an endogenous, inducible suppressor of systemic inflammation. In humans, stimulation with a TLR7/8 adjuvanted RNA-lipoplex (RNA-LPX) vaccine results in the secretion of inflammasome-activated interleukin-1β (IL-1β) by monocytes. Remarkably, IL-1β was found to control the induction of the broad spectrum of pro-inflammatory cytokines (including IL-6) associated with CRS. Unlike humans, murine leukocytes preferentially upregulate anti-inflammatory IL-1ra relative to IL-1β. IL-1ra deletion in mice leads to CRS-like symptoms, indicating that high levels of IL-1ra protect mice from uncontrolled systemic inflammation. Our results demonstrate that IL-1β and IL-1ra are key regulators that control systemic responses to RNA vaccines and other inflammatory stimuli. These data provide an explanation for the dramatic difference in dose-dependent tolerability between mice and humans and suggest an approach to evaluate pathogen-induced or immunotherapy-related inflammatory toxicities in vivo.

scholarly journals Evaluation of clinical symptoms and sonographic characteristics of femoral trochlear cartilage in primary knee osteoarthritis

2019 ◽  
Vol 6 (1) ◽  
pp. 18-22
Author(s):  
Bita Abbasi ◽  
Masoud Pezeshki-Rad ◽  
Mozhdeh Amini ◽  
Mahdi Foroughian ◽  
Maryam Sahebar ◽  
...  
Keyword(s):  
Physical Activity ◽  
Clinical Symptoms ◽  
Cross Sectional Study ◽  
Meniscal Extrusion ◽  
Baker’S Cyst ◽  
Cross Sectional ◽  
Knee Oa ◽  
Baker's Cyst ◽  
American College Of Rheumatology

Objective: This study was designed to evaluate the clinical symptoms and sonographic characteristics of femoral trochlear cartilage in patients with knee joint osteoarthritis (OA). Methods: This cross-sectional study was conducted on 94 patients with painful primary knee OA according to the American College of Rheumatology criteria with a visual analog scale pain score of 30 mm or more. Clinical features were evaluated by a rheumatologist according to the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) criteria, and a radiologist performed ultrasonography within a week. The thickness and echogenicity grade of three cartilage regions were evaluated. Other findings such as meniscal extrusion, effusion, and Baker’s cyst were recorded. Results: The average age of patients was 60 years. The linear regression model showed a significant association of grades II and III trochlear cartilage injury with the pain index, physical activity, and WOMAC overall index. However, there was no significant association between the trochlear cartilage thickness in these three regions and the WOMAC indexes (including pain, physical activity, and the overall index). There was also no significant association between Baker’s cyst and the WOMAC indexes, but a significant association was found between meniscal extrusion and the WOMAC index (P≤0.001). Conclusion: According to our study, the echogenicity grade determined by ultrasonography of femoral trochlear cartilage affects the clinical symptoms of patients including pain. These findings indicate the role of this diagnostic device in understanding changes due to the disease, and it can help physicians focus on the pathology in order to control clinical symptoms in patients.

Cyclic Compression of Chondrocytes Counteracts Pro-Inflammatory Tissue Remodeling Induced by Interleukin-1

2008 ◽  
Author(s):  
A. E. DiTullio ◽  
S. Park ◽  
P. A. Torzilli ◽  
C. T. Chen
Keyword(s):  
Interleukin 1 ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Matrix Remodeling ◽  
Synovial Joint ◽  
Confined Compression ◽  
Cyclic Compression ◽  
Trauma Injury ◽  
Pro Inflammatory Cytokines ◽  
Inflammatory Tissue

Chondrocytes in tissue engineered constructs face challenging environments when first transplanted into a synovial joint, including high levels of compression/shear and pro-inflammatory cytokines. The joint level of interleukin 1 (IL-1) after trauma injury and in a repaired joint is acutely elevated. Matrix remodeling in tissue engineered constructs can be easily affected by the elevation and activation of aggrecanases (ADAMTS-4 and ADAMTS-5) and matrix metalloproteinases (MMPs) [2–4, 7–9, 11]. Several recent studies suggest that tensile loading and unconfined compression of chondrocytes has some anti-inflammatory effects against interleukin 1 (IL-1) by the downregulation of COX-2 and iNOS genes [1, 5, 6]. However, the role of loading in tissue repair at physiological levels is not clear. The objective of this study was to determine the effect of cyclic confined compression on the gene expression of MMPs and tissue inhibitors of metalloproteinases (TIMPs) in agarose-embedded chondrocytes in the presence of interleukin 1 (IL-1).

scholarly journals Physiological and Pathological Role of Circadian Hormones in Osteoarthritis: Dose-Dependent or Time-Dependent?

2019 ◽  
Vol 8 (9) ◽  
pp. 1415 ◽  
Author(s):  
Farhad Md. Hossain ◽  
Yunkyung Hong ◽  
Yunho Jin ◽  
Jeonghyun Choi ◽  
Yonggeun Hong
Keyword(s):  
Circadian Clock ◽  
Thyroid Stimulating Hormone ◽  
Cartilage Erosion ◽  
The Relationship ◽  
Dose Dependent ◽  
Different Levels ◽  
Pro Inflammatory Cytokines

Osteoarthritis (OA), the most common form of arthritis, may be triggered by improper secretion of circadian clock-regulated hormones, such as melatonin, thyroid-stimulating hormone (TSH), or cortisol. The imbalance of these hormones alters the expression of pro-inflammatory cytokines and cartilage degenerative enzymes in articular cartilage, resulting in cartilage erosion, synovial inflammation, and osteophyte formation, the major hallmarks of OA. In this review, we summarize the effects of circadian melatonin, TSH, and cortisol on OA, focusing on how different levels of these hormones affect OA pathogenesis and recovery with respect to the circadian clock. We also highlight the effects of melatonin, TSH, and cortisol at different concentrations both in vivo and in vitro, which may help to elucidate the relationship between circadian hormones and OA.

scholarly journals Down-Regulation of MiR-150 Alleviates Inflammatory Injury Induced by Interleukin 1 via Targeting Kruppel-Like Factor 2 in Human Chondrogenic Cells

2018 ◽  
Vol 47 (6) ◽  
pp. 2579-2588 ◽  
Author(s):  
Xirui Yang ◽  
Qi Zhang ◽  
Zhaomeng Gao ◽  
Chunyan Yu ◽  
Lei Zhang
Keyword(s):  
Cell Viability ◽  
Inflammatory Cytokines ◽  
Cell Damage ◽  
Interleukin 1 ◽  
Annexin V ◽  
Cartilage Degeneration ◽  
Joint Injury ◽  
Notch Pathways ◽  
Induced Apoptosis ◽  
Pro Inflammatory Cytokines

Background/Aims: Interleukin-1 (IL-1) is known to be involved in cartilage degeneration following joint injury or due to osteoarthritis. In the present study, we explored the effects of miR-150 on IL-1-stimulated human chondrogenic cells ATDC5. Methods: ATDC5 cells were transfected with the mimic, inhibitor or negative controls specific for miR-150, and subsequently treated by IL-1. CCK8 assay, PI and FITC-conjugated Annexin V double-staining, Western blot, qRT-PCR and ELISA assay were performed to determine the changes of cell viability, apoptosis, and the release of pro-inflammatory cytokines. Targeting relationship between miR-150 and KLF2 was detected by dual luciferase activity assay. Results: IL-1 reduced cell viability, induced apoptosis, and enhanced the expression and release of pro-inflammatory cytokines (IL-6, IL-8 and TNF-α) in ATDC5 cells. IL-1 also increased the expression of miR-150. Suppression of miR-150 alleviated IL-1-induced cell damage in ATDC5 cells, while overexpression of miR-150 resulted in an opposite impact. KLF2 was negatively regulated by miR-150, and it was proved as a target gene of miR-150. KLF2 overexpression exhibited protective actions in IL-1-injured ATDC5 cells, even if miR-150 was suppressed in cell. Moreover, IL-1-induced activation of NF-kB and Notch pathways was alleviated by KLF2 overexpression. Conclusions: Suppression of miR-150 led to up-regulation of KLF2, which in turn protected ATDC5 cells against IL-1-induced injury.

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